ImmunoGen Inc (IMGN) 2020 Q4 法說會逐字稿

Good morning, and welcome to ImmunoGen's Fourth Quarter and Full Year 2020 Financial and Operating Results Conference call. Today's conference is being recorded. At this time, I'd like to turn the call over to Courtney O'Konek, Senior Director of Corporate Communications and Investor Relations. Please go ahead.

Good morning, and thank you for joining today's call. Earlier today, we issued a press release that includes a summary of our recent progress and fourth quarter and full year 2020 financial results. This press release and a recording of this call can be found under the Investors and Media section of our website at immunogen.com.

With me today are Mark Enyedy, our President and CEO; Anna Berkenblit, our Chief Medical Officer; and Susan Altschuller, our CFO. During today's call, we will review key accomplishments for the business over the last 12 months, our financial results and highlight upcoming anticipated events.

During the discussion, we will use forward-looking statements, and our actual results may differ materially from such statements. Descriptions of the risks and uncertainties associated with an investment in Immunogen are included in our SEC filings.

And with that, I'll turn the call over to Mark.

Thanks, Courtney. Good morning, everyone, and thank you for joining us today. Despite the challenges of the pandemic, 2020 was a transformative year for ImmunoGen as we adjusted to new ways of working, advanced our portfolio, strengthened our management team and balance sheet and positioned the business for 2 potential product launches next year.

Just to expand on a few of these points, beginning with our lead program, mirvetuximab in ovarian cancer. As a reminder, our goals for this program are to obtain initial approval as monotherapy in patients with platinum-resistant disease in 2022 and to expand into earlier lines of therapy with an emphasis on combination regimens. We made significant progress towards each of these objectives over the last year. With our monotherapy program, we expect to deliver top line results in the third quarter and to submit the BLA by the end of this year to support accelerated approval in 2022.

For our combination studies, we presented impressive data at both ASCO and ESMO last year, demonstrating that mirvetuximab has the potential to serve as the combination agent of choice in both platinum-sensitive and platinum-resistant ovarian cancer. Anna will cover these results in more detail later in the call.

With the benefit of the data generated thus far, we believe there is the potential to obtain compendia listings for combination use of mirvetuximab in close proximity to our initial monotherapy approval.

Turning to our second pivotal program, IMGN632, which is our CD123-targeting ADC. We were pleased to receive Breakthrough Therapy designation in relapsed/refractory BPDCN in the fourth quarter and to align with FDA on a path to support potential full approval in patients with BPDCN. Updated data presented at ASH 2020 demonstrated the encouraging antitumor activity and favorable safety profile we've seen with 632 in the clinic and increase our confidence in its potential to become the best-in-class treatment option for patients with BPDCN.

In addition to our late-stage portfolio, our pipeline includes 2 additional innovative ADCs. In November, we enrolled the first patient in the Phase I dose escalation study of IMGC936, which we are codeveloping with MacroGenics. 936 is a first-in-class ADC directed to ADAM9, which is a novel target expressed on a wide range of solid tumors. In tandem, we advanced our next-generation anti-FR alpha ADC, IMGN151 into preclinical development. 151 integrates innovation in each of the 3 components of the ADC, which should allow us to address patient populations with lower levels of FR alpha expression, including tumor types outside of ovarian cancer.

A key element of our strategy is partnering where we made notable progress in 2020 with our agreement with Huadong Medicine to develop and commercialize mirvetuximab in Greater China. This collaboration is off to a strong start with Huadong recently receiving acceptance of an IND application for mirvetuximab in China from the NMPA.

Finally, through a combination of business development and activity under our ATM facility, we added more than $140 million to our balance sheet in the fourth quarter. On the strength of our performance in 2020, we are excited about the year ahead with several important milestones. As I mentioned earlier in the call, for mirvetuximab, we expect to report top line data for SORAYA in the third quarter, followed by a submission by the end of the year. We also anticipate sharing final data from the FORWARD II doublet cohort evaluating mirvetuximab in combination with bevacizumab in recurrent ovarian cancer at ASCO in June.

For IMGN632, we expect to complete enrollment and share top line data for our pivotal frontline cohort in the Phase I/II BPDCN study in 12 to 18 months. We also plan to report data from our combination regimens evaluating IMGN632 with azacitidine and/or venetoclax in patients with relapsed/refractory and frontline AML at ASH. For IMGC936, we will continue to enroll patients in the Phase I dose escalation study and anticipate initial data late this year or early next. And for IMGN151, we plan to submit the IND by year-end. So with a full calendar of important events, we look forward to a productive 2021.

With that, I'll turn the call over to Anna to provide some additional color on our clinical programs. Anna?

Thanks, Mark. We have covered the ongoing progress and upcoming milestones for our mirvetuximab monotherapy program. So I'll direct my comments this morning to our combination studies.

Starting with the mirvetuximab plus bevacizumab combination. We presented initial efficacy and safety data of the doublet from our Phase Ib FORWARD II study in platinum-agnostic recurrent ovarian cancer in an oral session at ASCO 2020. We are particularly encouraged by the overall response rate of 64% observed in patients with high FR alpha expression regardless of platinum status and look forward to the continued evaluation of mirvetuximab with bevacizumab in this growing population of recurrent ovarian cancer patients for whom a nonplatinum-based regimen would be appropriate. As Mark mentioned, we plan to present mature data from this study at ASCO this year.

We also presented final data from our FORWARD II triplet cohort, evaluating mirvetuximab in combination with carboplatin and bevacizumab at ESMO 2020. In this cohort of patients with medium or high levels of folate receptor alpha, we observed a confirmed overall response rate of 83% with a median duration of response of 10.9 months and a median progression-free survival of 12.8 months. These efficacy data are noteworthy as the population enrolled is more heavily pretreated, with a greater percent of patients having had more than 1 prior line of therapy as well as more prior targeted therapies, including bevacizumab and PARP inhibitors, than in previously published triplet trials in recurrent platinum-sensitive ovarian cancer.

Going forward, we will be supporting 2 investigator-sponsored trials to generate additional data for the mirvetuximab plus carboplatin doublet this year: a randomized Phase II study of about 140 patients in recurrent platinum-sensitive ovarian cancer and a 70-patient neoadjuvant study. Having generated a wealth of data demonstrating encouraging efficacy and favorable tolerability, mirvetuximab continues to show promise in combination. In addition to the potential for compendia listing, contemporaneous with mirvetuximab's initial approval, we are working to define a formal path to label expansion for mirvetuximab.

Moving to IMGN632. Having received breakthrough designation and alignment on a path to full approval in BPDCN with FDA, we are enrolling up to 20 patients in the pivotal frontline cohort of the Phase I/II study of IMGN632 in BPDCN and expect to complete enrollment and generate top line data in 12 to 18 months. Notably, we have previously enrolled 3 patients who meet the frontline eligibility criteria and have observed clinical complete responses in all 3 of these patients. While we are unable to count these patients towards our prospective cohort of 20 patients, these data are encouraging.

At ASH in December last year, we presented updated safety and efficacy findings from the Phase I/II study of IMGN632 in patients with relapsed/refractory BPDCN. These data demonstrated an overall response rate of 29% in all relapsed/refractory patients. This activity demonstrates the potential for IMGN632 particularly in patients who received prior intensive therapy, including those who received prior tagraxofusp-erzs. Importantly, IMGN632 has a favorable safety profile without capillary leak syndrome, drug-related discontinuations or drug-related deaths and with a 0% 30-day mortality rate. Accordingly, it is well tolerated as a brief outpatient infusion once every 3 weeks without need for hospitalization for initial administration. Taken together, the safety, efficacy and convenience of IMGN632 reinforce the potential of this CD123-targeting ADC as a best-in-class treatment option for BPDCN patients.

Also at ASH, our collaborators at MD Anderson Cancer Center presented preclinical data in relapsed/refractory AML that further support the combination of IMGN632 with azacitidine and venetoclax. In AML cell lines and patient-derived xenograft models, the triplet has demonstrated synergistic cell death with the potential to overcome resistance to VEN-AZA and superior antileukemia activity over both VEN-AZA as a doublet and IMGN632 monotherapy. These data further support the addition of ACD123 targeted ADC with a novel DNA-damaging payload to standard of care in AML.

Our Phase Ib/II 802 study is designed to determine the safety, tolerability and preliminary antileukemia activity of IMGN632 when administered in combination with azacitidine and/or venetoclax to patients with relapsed and frontline CD123 positive AML. The study is in the dose escalation phase and enrolling relapsed and refractory patients to determine the recommended Phase II dose of IMGN632 in combination. We continue to observe encouraging initial antileukemia activity and a well-tolerated safety profile without dose-limiting toxicity observed in the triplet.

We look forward to the continued evaluation of the IMGN632 triplet and anticipate sharing data from this study at ASH once we have identified a recommended Phase II dosing schedule for the combination for further study. We also continue to evaluate IMGN632 as monotherapy in minimal residual disease positive AML.

With that, I'll turn the call over to Susan to cover our financials. Susan?

Thanks, Anna. Starting with our results for the full year 2020. We generated $132.3 million in revenue, $68.5 million of which came from noncash royalty revenues. The remainder coming from license and milestone fees, which include recognition of $60.5 million from the upfront fee previously received under the collaboration with Jazz.

Operating expenses were $154.7 million, comprised of $114.6 million of R&D expenses compared with $114.5 million in 2019. G&A expenses were $38.6 million compared to $38.5 million in 2019. In addition, we incurred a $1.5 million restructuring charge comprised substantially of retention costs. We ended 2020 with $293.9 million in cash on the balance sheet. Subsequent to year-end, in January, we sold an additional 4.5 million shares of common stock through our ATM facility, generating additional gross proceeds of approximately $35 million.

Turning to our financial guidance for 2021. We expect revenues to be between $65 million and $75 million. Operating expenses between $200 million and $210 million and cash and cash equivalents at year-end to be between $140 million and $150 million. This provides us with sufficient runway to fund operations into the second half of 2022.

I'll point out that revenue guidance includes the assumption that a portion of the $40 million upfront license fee from Huadong Medicine will be recognized in 2021 as the upfront fee will be amortized over time as clinical supply requirements are delivered. In addition, ImmunoGen expects its noncash royalty revenues to reduce starting in the second half of this year based on the terms of prior royalty transactions for Kadcyla.

With that, I will turn the call over to Mark for closing comments. Mark?

Thanks, Susan. So after a transformative 2020, we entered this year with significant momentum and strong prospects for the business. With an important near-term pivotal readout for our lead program, a second pivotal program with data in 12 to 18 months, our earlier-stage portfolio accelerating and a strong cash position to carry us past our first approval, we have the right strategy, team and resources in place to generate value in the near and long-term as we transition to a fully integrated oncology company and bring our first 2 products to market in 2022.

With that, we'll open the call for questions.

(Operator Instructions) Our first question comes from John Newman from Canaccord.

Just have two quick questions here. The first one, for the FORWARD I study for mirvetuximab, I believe you had previously overenrolled that study a bit. Obviously, I know that things are difficult and different in the COVID environment, but I'm just curious if -- whether you would be open to some additional patient enrollment for SORAYA if the demand is there.

Thanks, John. So we over enrolled FORWARD I by about 10%, which is really the upper limit that's considered acceptable when you're thinking about study designs. You want to enroll the patients to answer the question that you set out to answer. It turned out that with FORWARD I, enrollment at the end was very brisk. And so it worked out to patients' benefit because there were patients who met all the eligibility criteria, had consented. And thankfully, we were able to accommodate about 10% more than we had originally designed the study for. I wouldn't be surprised if the same occurs with SORAYA and MIRASOL.

Great. And the second question I have, regarding compendia listing -- potential compendia listing for mirvetuximab combination therapy, just curious how soon after mirvetuximab approval as a monotherapy might you be able to file for that compendia listing.

Yes, almost immediately, John. So what's required is 2 peer-reviewed publications. And so the expectation is to get the results of the 2 cohorts that we've run so far with mirv and bev into journals and then use that as the basis for the submission. But the expectation is to move very quickly following the initial approval to work with the compendia to have those studies included in their treatment guidelines.

Our next question comes from Michael Schmidt from Guggenheim Securities.

This is Yige Guo on for Michael. Congrats on the progress. Our first question is on mirvetuximab. Maybe can you provide any color on the mirv-Avastin combo maturity that's to be presented at ASCO? And since there isn't a known standard of care treatment for platinum-agnostic ovarian cancer, how should we think of the efficacy bar in this population to inform the next step?

Yes. So as a reminder, last year, Lucy Gilbert at ASCO presented data for the platinum-agnostic cohort of mirvetuximab plus Avastin. And in the FR alpha high population, confirmed overall response rate was 64% in patients with platinum-resistant disease. So in that subset, the response rate was 59%. And in the platinum-sensitive recurrent subset, it was to the tune of high 60s. Both of these numbers, these response rates, compare favorably to what you would see with standard of care in these populations. So for Avastin plus chemotherapy, the confirmed response rate is 27%, 28%. So the mirvetuximab plus Avastin data looked quite nice relative to that in the platinum-resistant disease.

Turning to recurrent platinum-sensitive disease, with platinum-based doublets with just 1 prior line of therapy, you typically get a response rate in the low 50s. And so our response rate in the 60s is quite nice when you think about the fact that we're not exposing patients again to platinum-based therapy. So I think this will give us really some nice options to consider as we think about the formal label expansion. And in the meantime, as you heard from Mark, we'll be solidifying the approach for a compendia listing.

Got it. And then the next question, on 632. You said you'll enroll up to 20 frontline patients to clear bar of 10% CR or CRi. Can you maybe elaborate a little on the potential scenario that you don't need to enroll all 20 patients to meet the primary end point? Or in other words, what would be the minimum number of patients you need in this cohort?

Sure. I would point you to ELZONRIS as a relevant regulatory precedent. When you look at their label, you will see that they received full approval based on their CR/CRc rate in 13 frontline BPDCN patients.

Our next question comes from Boris Peaker from Cowen.

My first question, I just wanted to ask for mirvetuximab. Can you talk about the manufacturing? Specifically, where is it manufacturing? Which companies are involved? And what other steps are required to do in manufacturing, whether it's assay validation or any kind of studies prior to submitting the BLA?

Sure. So you all recall the 3 components to an ADC, together with the conjugation step to bring each of those components together. So the antibody is produced by Boehringer Ingelheim. The linker is produced at SAFC, Sigma-Aldrich, and the payload is produced by Teva-Sicor and then we use BFP for the conjugation steps. So we're in good shape in terms of validation for mirvetuximab. We have all of the relevant assays in place. And so we should be in good shape in terms of at the time that we're ready for inspection following a BLA submission for those facilities.

Great. And my last question is on 632 in BPDCN. I'm just curious kind of what your take is on how it'll compete with ELZONRIS commercially if approved.

Yes, we would compete, I think, on the basis of the key parameters of the pharmaceutical commercialization. So those are efficacy, safety, patient convenience. And I think that based on the data we've generated to date, we're going to compare quite favorably, particularly as it relates to safety and convenience, looking at their label versus that we've generated to date. All the relevant parameters there I do think tilt in our favor based on the data we generated to date. If you look at ELZONRIS, a patient is required to be admitted into a hospital for at least 5 days to initiate therapy, treatment with 632, the 30-minute outpatient infusion. So on all the parameters, the emerging profile we see is we think, will compare quite favorably, and that would be the basis for competition.

Our next question comes from Andy Hsieh from William Blair.

Great. I very much look forward to a very eventful 2021. So I just have a couple of questions for Anna in terms of kind of framing expectations for ASCO. So first off, would this be the same 60 -- roughly 60-patient population with longer follow-up at ASH this year?

Yes, Andy. So I probably should have mentioned that when the previous question was asked. Yes, it's the same number of patients. And what you will see in addition to ORR data, which we shared last year, you will now see duration of response data and PFS data now that we've been following patients for a longer period of time. And we remain quite encouraged about the potential for this combination.

Great. And do you mind reminding me -- so I believe there were about 40% of the patients who had previous Avastin. Did you see a higher efficacy activity in Avastin-naive patients among the 60 enrolled?

When we looked at that, Andy, it was kind of hard to tease apart because Avastin use was also correlated with a number of priors. So given the small data set, you couldn't pick them apart.

Okay. Yes, that makes sense. And then for the 2 ISTs, I didn't really catch that. So did you say that -- the 145 patients and then 70-patient neoadjuvant study, did you say those are progressing well and could have data soon?

So these 2 ISTs are exploring mirvetuximab plus carboplatin. We have very encouraging data from our Phase I dose escalation study for the doublet. It looks basically like the mirv-carbo doublet performs like you would expect for a platinum-based triplet without the bevacizumab. So on the basis of those encouraging preliminary data, 2 investigators came to us with ideas for further exploration of this mirv-carbo doublet. The first is Dr. Harter in Germany. We're working with the AGO, and they're doing a randomized Phase II of mirv plus carbo, with mirvetuximab continued -- held back as maintenance versus standard platinum-based therapy with or without maintenance in recurrent platinum-sensitive setting. And that study is getting up and running.

Similarly, [Rebecca Arndt] at Ohio State came to us with a new adjuvant concept that's being run at several centers in the U.S. here. And this is really the first opportunity for us to get mirvetuximab into the frontline setting. And so that's the 70 patients, really a feasibility study with some translational and correlative science built in, and that also is getting up and running. I think I can't speak for the investigators regarding when data will be available.

Our next question comes from Kennen MacKay from RBC Capital Markets.

Congrats on the progress in 2020. I guess, first, would love to understand how you're thinking about sort of a commercial build ahead of anticipated BLA filing in sort of the back half of the year, if you'll be returning to sort of the pre-hiring strategy utilized previously, again, just how you're thinking about that. And then secondly, ahead of the IND for 151, just wanted to sort of understand your perspective on the unmet need that, that antibody is addressing versus mirv or other prior fully targeted ADCs or small molecules.

Sure. I'll start with the commercial planning and then hand it over to Anna to talk about 151. So this is a relatively concentrated market, Kennen, when you think about physician targets and referral patterns and the like. And so we think that the commercial -- the investment required to support a robust launch will be well within our ability to finance and manage. And so our effort at this point are concentrated more on market research, understanding, physician-patient segmentation, where these patients are, payer mix, those kinds of issues. And once we have the benefit of the SORAYA readout, we would move in earnest in terms of recruiting a sales force, sales management and the like.

In parallel with that, we, of course, are developing a distribution plan, again, working with some outside support to define how we will approach distribution, again, with the goal of lining up vendors that we could move forward to definitive agreements with -- post the SORAYA readout. So as we think about spend for this year, we will see some expenditures in the earlier parts of the year as we worked through some of these planning exercises and then a significant expenditure with the benefit of a positive readout and certainly ramping heavily in the fourth quarter of this year in anticipation of the filing and approval in 2022.

So let me just pause and ask you if you have any follow-up there. And if not, I'll turn it over to Anna.

No, that's really helpful. Appreciate that color.

So turning to IMGN151, which is our next-generation biparatopic FR alpha targeted ADC. We've really designed it to address a broader population of FR alpha positive tumors. And we've done that by targeting 2 separate epitopes in folate receptor alpha which allows greater internalization events and greater cell killing. We also have a stable linker peptide combination that allows for even greater stability in the circulation than with mirvetuximab. And the payload itself, DM21, is a bit more hydrophobic. So once the ADC is internalized, you get even more bystander killing, which can help with some of the heterogeneity of FR alpha expression.

So with that in mind, we anticipate that IMGN151 can address the broader population of patients with FR alpha positive tumor. So not just the 40% whom we know benefit from mirvetuximab, but with FR alpha high expression, but also the 40% additional FR alpha positive tumors with low or medium expression because we know about 80% of ovarian cancers have FR alpha expression. So that should really double the population for ovarian cancer. And then moving to other tumor types, endometrial cancer, triple-negative breast cancer and lung cancer, it's a little premature to say what the appropriate cutoffs will be for those indications for patient selection but we're confident, given the preclinical data we've generated thus far, that the potential for IMGN151 is much broader than that of mirvetuximab.

Our next question comes from Jessica Fye from JPMorgan.

This is Luke on for Jess. I guess to start, can you give us an idea of what sort of level of detail we can expect between the top line readout for SORAYA in 3Q versus data coming later this year?

A little hard to say right now, Luke, because we are able to pretty accurately assess when we'll have sufficient data for confirmed overall response rate by investigator, which is our primary end point. Duration of response, as you know, needs to mature over time. And the better patients are doing on mirvetuximab and SORAYA, the longer median duration of response will be. And so when we have material data, we will share it.

Okay. And then also, is there any additional color you guys can give us on the Huadong licensing fee? Should we expect that to be amortized sort of over the entire year, longer than that, shorter than that? When can we see those revenues totally recognized?

Yes. As we mentioned in our filing, the $40 million Huadong on upfront license fee will be recognized over time as clinical supply requirements are delivered. So our 2021 revenue guidance includes an estimated amount of the fee that will be amortized based on the current supply plan. Our estimate would be that potentially up to half of the fee could be recognized in 2021. But again, it's dependent on the supply plan, which will continue to be refined as Huadong determines its regulatory strategy.

And our next question comes from Biren Amin from Jefferies.

Maybe just one more on IMGN151. I think with this compound, you're also seeing an increase in conjugate exposure by 40% over mirv, and I think this has also a higher half-life than mirv. So Anna, maybe, how are you thinking about the safety profile of 151 as it compares to mirv, in particular, the ocular tox as you file the IND by year-end?

Yes. So Biren, again, it's a little early to speculate, but the ocular adverse events that are seen with tubulin-directed payloads, so including Abraxane and then ADCs with tubulin-directed payloads, including oral statins and maytansinoid, I think it's reasonable to anticipate that there will be some ocular adverse events with IMGN151, but it's not clear to me that it's linked in any regard to half-life specifically. So I think we're doing the preclinical data that we need to do to support the IND. And we've also really figured out how to optimally manage the ocular adverse events with mirvetuximab. So we'll apply those lessons learned for when we consider patient study design in terms of lubricating eye drops and things like that.

And maybe just a follow-up on that. Are you seeing anything in your preclinical animal model studies with 151 as it relates in comparison to mirv in terms of just toxicity?

Not at this point.

Our next question comes from Jonathan Chang from SVB Leerink.

Just one for me. Given the proximity of the potential SORAYA BLA filing and the MIRASOL data readout, can you talk about the risk, if any, that the regulators may want to see the results of MIRASOL before potentially approving mirvetuximab?

Yes. We get this question fairly often. The answer is this, if the readout for SORAYA is positive and the data meets the criteria for accelerated approval, which, in this case, would mean that the ORR and the DOR surpass that of available therapy, there is no basis for the FDA to delay regulatory action.

Our last question comes from Swayampakula Ramakanth from H.C. Wainwright.

Most of my questions have been answered but just have -- trying to understand what your commercialization strategy is in Europe for both mirv and also 632?

Sure. So in both cases, again, these are highly concentrated markets, meaning the physician targets are limited. And so commercial investments are modest and certainly something that we could undertake with our own financing. So we are evaluating those markets. We have a little bit of time as it relates mirvetuximab. We think that the EU will likely require the outcome of MIRASOL as a basis for approval. We'll talk to them about the SORAYA data, but our expectation is they probably will want the results of a randomized controlled study to support approval. So we will revisit this over the course of the latter part of this year and into 2020. But again, both of those products could be commercialized by ImmunoGen, and we could support a robust launch in the markets in Europe.

And that does conclude our question-and-answer session for today's conference. And I'd like to turn the conference back over to Mark Enyedy for any closing remarks.

Great. Well, thank you all for the questions this morning. We're excited about the year ahead, and we'll look forward to reporting our progress in subsequent calls and around our major data presentations. Thanks.

Ladies and gentlemen, this concludes today's conference call. Thank you for your participation, and you may now disconnect. Everyone, have a wonderful day.